Improving Viral Protease Inhibitors to Counter Drug Resistance
Department of Biochemistry and Molecular Pharmacology
Biochemistry | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Structural Biology | Virology
Drug resistance is a major problem in health care, undermining therapy outcomes and necessitating novel approaches to drug design. Extensive studies on resistance to viral protease inhibitors, particularly those of HIV-1 and hepatitis C virus (HCV) protease, revealed a plethora of information on the structural and molecular mechanisms underlying resistance. These insights led to several strategies to improve viral protease inhibitors to counter resistance, such as exploiting the essential biological function and leveraging evolutionary constraints. Incorporation of these strategies into structure-based drug design can minimize vulnerability to resistance, not only for viral proteases but for other quickly evolving drug targets as well, toward designing inhibitors one step ahead of evolution to counter resistance with more intelligent and rational design.
DOI of Published Version
Trends Microbiol. 2016 Apr 15. pii: S0966-842X(16)30002-6. doi: 10.1016/j.tim.2016.03.010. [Epub ahead of print] Link to article on publisher's website
Trends in microbiology
Yilmaz NK, Swanstrom RI, Schiffer CA. (2016). Improving Viral Protease Inhibitors to Counter Drug Resistance. Schiffer Lab Publications. https://doi.org/10.1016/j.tim.2016.03.010. Retrieved from https://escholarship.umassmed.edu/schiffer/11